ArticleCell2023
Humanized mouse liver reveals endothelial control of essential hepatic metabolic functions.
Article in Cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Regulatory Mechanisms Within Multicellular Signaling Networks in Liver Ischemia-Reperfusion Injury: A Systematic Review Focusing on Cell-Type-Specific Interactions.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Pooled it
- Reverse genetics in humanized mice reveals CARD8-mediated pyroptosis causing pancytopenia in human DPP9 deficiency.The Journal of clinical investigation · 2026Article
- Functional editing of the OTC locus by targeted integration with phenotype correction and restoration of endogenous expression patterns.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Hepatic metabolic adaptation to endurance exercise: temporal and sex differences by multiomics integration and validation.Cell communication and signaling : CCS · 2026Article
- The making of cells and organs in xenogeneic animal bioreactor.Signal transduction and targeted therapy · 2026Review
- With no lysine kinase 1 in hepatic stellate cells promotes mouse and human liver fibrosis through glycolytic triosephosphate isomerase 1.Hepatology (Baltimore, Md.) · 2026Article
- Reverse genetics in humanized mice reveals CARD8-mediated pyroptosis causing pancytopenia in human DPP9 deficiency.bioRxiv : the preprint server for biology · 2026Article
- Advancement of humanized mice and leading applications in immunological disease models.Inflammation and regeneration · 2026Review
- Research progress and development strategies of antibody-oligonucleotide conjugates.Gene therapy · 2026Review
- Fibroblast growth factor 10 attenuates advanced liver fibrosis through hepatocyte fibroblast growth factor receptor 2 signalling.Clinical and translational medicine · 2026Article
- Balancing cholesterol metabolism in the liver and gut: perspectives in health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Recent advances in the construction of humanized animal models and applications in translational medicine.Animal models and experimental medicine · 2026Review
- Metabolic dysfunction-associated steatotic liver disease and steatohepatitis-associated hepatocarcinoma preclinical models.Nature reviews. Gastroenterology & hepatology · 2026Review
- Long-term multi-organ system abnormalities in mice exposed to antenatal and postnatal corticosteroids.Pediatric research · 2026Article
- Endothelial Cell Therapy for the Acute and Chronic Liver Disease.Seminars in liver disease · 2026Review
- Patient-Derived Models of Liver Cancer to Inform Clinical Treatment Paradigms: Recent Updates.Seminars in liver disease · 2026Review
- Article
- Hic-5 promotes the progression of nonalcoholic steatohepatitis by regulating hepatocellular fatty acid metabolism through the PTEN/PGE2/EP4 axis.Molecular biomedicine · 2026Article
- hLMR1, a hepatocyte-specific long noncoding RNA that represses amino acid catabolism through pre-mRNA interaction in human liver.PloS one · 2026Article
- Integrated multi-omics, spatial profiling and organoid modeling drive transformative advances in chronic liver disease and hepatocellular carcinoma immunomicroenvironment research.Frontiers in immunology · 2026Review
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Hepatocytes, the major metabolic hub of the body, execute functions that are human-specific, altered in human disease, and currently thought to be regulated through endocrine and cell-autonomous mechanisms. Here, we show that key metabolic functions of human hepatocytes are controlled by non-parenchymal cells (NPCs) in their microenvironment. We developed mice bearing human hepatic tissue composed of human hepatocytes and NPCs, including human immune, endothelial, and stellate cells. Humanized livers reproduce human liver architecture, perform vital human-specific metabolic/homeostatic processes, and model human pathologies, including fibrosis and non-alcoholic fatty liver disease (NAFLD). Leveraging species mismatch and lipidomics, we demonstrate that human NPCs control metabolic functions of human hepatocytes in a paracrine manner. Mechanistically, we uncover a species-specific interaction whereby WNT2 secreted by sinusoidal endothelial cells controls cholesterol uptake and bile acid conjugation in hepatocytes through receptor FZD5. These results reveal the essential microenvironmental regulation of hepatic metabolism and its human-specific aspects.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.